Vanishing White Matter Disease Presenting as Dementia and Infertility: A Case Report

OBJECTIVES: Vanishing white matter (VWM), an inherited leukoencephalopathy affecting the brain and the spinal cord, is most often a childhood-onset progressive disorder, generally presenting with ataxia. The adult-onset VWM is relatively rare with slowly progressive cognitive dysfunction dominating the clinical presentation. We report a case of adult-onset VWM from the Indian subcontinent. METHODS: Exome sequencing. RESULTS: A 58-year-old woman with young-onset diabetes and hypertension presented with gradually progressive cognitive decline beginning at age 40 years. She had early and predominant executive dysfunction and emotional lability and late involvement of memory and navigation. In addition to cognitive dysfunction, the patient experienced bladder and bowel incontinence along with a spastic gait. She also had primary infertility and menopause at age 40 years. Two of the patient's sisters had primary infertility; one of them had urine and stool incontinence along with gait disturbance. An MRI examination of the brain showed diffuse, symmetrical T2/fluid-attenuated inversion recovery white matter hyperintensities. On genetic testing, the patient was found to be homozygous for c.687T>G variation in the EIF2B3 gene. DISCUSSION: Adult-onset VWM is rare. Infertility in an adult patient with progressive cognitive decline should raise a suspicion of VWM.